Our daughter called tonight to say she had seen on the news where there was a study done in Parkinson's patients starting 4 years ago. This study was done using the own individual's stem cells and evidently was quite a success. She said people with Parkinsons who could not do much 4 years ago can now live decently. She said it was not a cure but enabled Parkinsons patients to live a decent life. She also said this study should be a help for many others disorders which should include HD.

What good news!!

This study used "gene therapy". I neglected to mention that.

Using one's own cells to combat HD would not work, would it?

Those cells would have the defective gene.

The Parkinson's study didn't involve stem cells, it involved gene therapy. (FRED, THIS IS THE STUDY YOU'VE BEEN FOLLOWING.) What is good about it for the HD community is that a lot was learned about delivery and there were no side effects from the procedure.
_______

Promising results from first gene therapy clinical trial for Parkinson's disease reported

Patients' motor skills improved with no major side effects, Weill Cornell team reports

NEW YORK (June 21, 2007) -- In what could be a breakthrough in the treatment of neurological disease, a team led by physician-scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center has completed the first-ever phase 1 clinical trial using gene therapy to battle Parkinson's disease.

The study of 11 men and one woman with the progressive neurodegenerative illness found that the procedure -- in which surgeons inject a harmless gene-bearing virus into the brain -- was both safe and resulted in improved motor function for Parkinson's patients over the course of one year. The findings are published in the June 23 issue of The Lancet.

"These exciting results need to be validated in a larger trial, but we believe this is a milestone -- not only for the treatment of Parkinson's disease, but for the use of gene-based therapies against neurological conditions generally," says lead researcher Dr. Michael Kaplitt, associate professor of neurological surgery and the Victor and Tara Menezes Clinical Scholar in Neurological Surgery at Weill Cornell Medical College, and director of Movement Disorders Surgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

Dr. Kaplitt has devoted much of his academic research career to the development of effective gene therapy techniques against Parkinson's disease and other neurological disorders. In fact, 13 years ago, he and Dr. Matthew During pioneered a now widely used gene-delivery technique for the brain using an altered, harmless form of adeno-associated virus (AAV). In 2003, Dr. Kaplitt performed the world's first gene therapy surgery for Parkinson's, conducted at NewYork Presbyterian/Weill Cornell.

"Viruses exist in nature mainly to transfer their own genes to the host cell," he explains. "So, we modify the AAV in such a way that the only gene it carries is the one we want to deliver to the therapeutic site."

In this case, the "gene of interest" is the glutamic acid decarboxylase (GAD) gene. "GAD makes a chemical called GABA, a major inhibitory neurotransmitter in the brain that helps 'quiet' excessive neuronal firing," explains Dr. During, the senior author of the current study, who worked on this research while at Weill Cornell. Dr. During is now professor of molecular biology and cancer genetics at Ohio State University.

"In Parkinson's disease, not only do patients lose many dopamine-producing brain cells, but they also develop substantial reductions in the activity and amount of GABA in their brains. This causes a dysfunction in brain circuitry responsible for coordinating movement," Dr. During explains.

The researchers' bold idea: to insert the GABA-producing gene GAD back into an area of the brain called the subthalamic nucleus, a key regulatory center within this motor circuit.

"Our hope was that with a single operation to this single site, we could boost GABA production and thereby normalize the function of the entire circuit," Dr. Kaplitt says. "Not only would this alter the chemical balance in the subthalamic nucleus; it should also provide GABA to other parts of the network that weren't getting enough of the neurotransmitter."

To test that theory, the investigators injected the GAD-bearing AAV vector into the subthalamic nucleus of each of the 12 Parkinson's patients, but only on one side of their brains.

"Because this was the first such study of its kind, we targeted just one side of the brain initially out of concerns for the patients' safety," Dr. During says. "However, since the patients were symptomatic on both sides of the brain, this also provided an untreated side for comparison with the treated hemisphere."

The researchers then used a standard assessment of motor function, the Unified Parkinson's Disease Rating Scale (UPDRS) to track changes in patients' symptoms over the next 12 months. They also tracked changes in each patient's brain activity using positron emission tomography (PET) scans. These were both performed by the other two principal authors of the study, Drs. Andrew Feigin and David Eidelberg of North Shore-Long Island Jewish Health System.

"Like all phase 1 studies, this one was primarily focused on gauging the safety of the technique," Dr. Kaplitt says. "And on that count it succeeded brilliantly: We saw no adverse events related to the treatment, no immunological changes or infections over the year of the study, no imaging evidence of toxicity whatsoever."

The results in terms of clinical and neurological efficacy were also encouraging.

"In terms of the UPDRS scores measuring motor function, we observed significant improvements in the 'off-state' phase -- meaning that period when Parkinson's patients have been off their medicines for 12 hours -- and also in the on-medication phase, when they were taking their drugs," Dr. Kaplitt says.

For example, at three months post-treatment, the patients as a group had already charted between a 25- and 30-percent improvement in off-state UPDRS scores, and those improvements persisted over the full year of the study. Similar results were seen in the on-medication state, the researchers found. Several individual patients showed impressive improvements of between 40 percent and 65 percent.

"That was really surprising and heartening, because traditional Parkinson's surgeries improve patients in the off-state but not as frequently in the on-medication state," Dr. Kaplitt says.

"Interestingly, these improvements in motor function were due to the side of the body controlled by the brain hemisphere that had received the treatment," Dr. During notes. "Also, AAV tends to require several weeks to maximize and stabilize production of a therapeutic gene, and in fact we did not see significant clinical changes until more than 1 month after surgery. These both further suggest that it was the gene therapy that was driving their improvement."

There were also strong trends toward reductions in medication-linked dyskinesia (movement difficulties) and improved activities of daily living, although neither of these trends reached statistical significance.

Finally, PET scans revealed a more normal level of activity up to 1 year following surgery in exactly those areas of the brain that the researchers had been hoping to "fix." Again, this improvement "occurred only in that half of the brain that had received the GAD gene," Dr. Eidelberg says.

Will these remarkable improvements persist" Only longer follow-up can tell, but prior studies in animals, including primates, suggest that the transplanted gene does stay active for years, Dr. Kaplitt says.

"Our next step of course is to move towards a larger, more definitive efficacy-centered study," he notes.

"We believe that this breakthrough trial has implications that go far beyond Parkinson's research," Dr. Kaplitt adds. "It's taken us nearly two decades of hard work to get here, but the success of this trial lays the foundation for the use of gene therapy against neurological diseases generally. We've now shown that the genetic modification of the patient's own brain cells can be done safely, and it appears to have enough effectiveness in this case to justify further exploration -- potentially opening up gene therapy for a host of brain disorders."

Of special note to us:
"We believe that this breakthrough trial has implications that go far beyond Parkinson's research," Dr. Kaplitt adds. "It's taken us nearly two decades of hard work to get here, but the success of this trial lays the foundation for the use of gene therapy against neurological diseases generally. We've now shown that the genetic modification of the patient's own brain cells can be done safely, and it appears to have enough effectiveness in this case to justify further exploration -- potentially opening up gene therapy for a host of brain disorders."

The findings are published in the June 23 issue of The Lancet.

Marsha-
Thank you for the article. I had not seen it. I had corrected myself from stem cell to gene therapy and I thank you for posting the article.
I think it looks extremely promising along with a couple other promising trial going on!

I think that is great especially considering the Michael J. Fox Foundation has directed over 92 MILLION in funds to Parkinson's Research. The private sector has done a great job with so little.

Wow, that was an incredible article marsha, thank you, and thank you sharon for bring this up, very interesting and hopeful.

Here's a study using a similar technique for HD mice:
[www.ncbi.nlm.nih.gov]

"Emergence and progression of HD depend on continuous expression of mutant Huntingtin protein (Htt). Therefore, blocking expression of mutant Htt might be a promising therapeutic strategy. We generated a high-capacity adenoviral (HC-Ad) vector expressing a short hairpin RNA (shRNA) targeted to exon 1 of the htt gene. In vitro, this vector efficiently inhibited Htt expression in neuronal and nonneuronal cell lines. In addition, the number of Htt-immunoreactive (IR) aggregates, a hallmark of HD pathology, was significantly reduced after gene transfer with this vector. Importantly, the attenuation of aggregate formation by shRNA was observed in vivo after stereotaxic injection into the striatum of mouse models of HD. The vector was tested in two models: the R6/2 transgenic mouse model and a mouse model based on the local injection of an adenoviral vector expressing a truncated version of mutant Htt. In both models an efficient reduction in mutant Htt aggregate load measured by decreased Htt-IR aggregate formation was observed. Our results support the further development of shRNA for HD therapy."

Marsha Wrote:
-------------------------------------------------------
> The Parkinson's study didn't involve stem cells,
> it involved gene therapy. (FRED, THIS IS THE
> STUDY YOU'VE BEEN FOLLOWING.) What is good about
> it for the HD community is that a lot was learned
> about delivery and there were no side effects from
> the procedure.
> _______
>
> Promising results from first gene therapy clinical
> trial for Parkinson's disease reported
>
> Patients' motor skills improved with no major side
> effects, Weill Cornell team reports
>
> NEW YORK (June 21, 2007) -- In what could be a
> breakthrough in the treatment of neurological
> disease, a team led by physician-scientists at
> NewYork-Presbyterian Hospital/Weill Cornell
> Medical Center has completed the first-ever phase
> 1 clinical trial using gene therapy to battle
> Parkinson's disease.
>
> The study of 11 men and one woman with the
> progressive neurodegenerative illness found that
> the procedure -- in which surgeons inject a
> harmless gene-bearing virus into the brain -- was
> both safe and resulted in improved motor function
> for Parkinson's patients over the course of one
> year. The findings are published in the June 23
> issue of The Lancet.
>
> "These exciting results need to be validated in a
> larger trial, but we believe this is a milestone
> -- not only for the treatment of Parkinson's
> disease, but for the use of gene-based therapies
> against neurological conditions generally," says
> lead researcher Dr. Michael Kaplitt, associate
> professor of neurological surgery and the Victor
> and Tara Menezes Clinical Scholar in Neurological
> Surgery at Weill Cornell Medical College, and
> director of Movement Disorders Surgery at
> NewYork-Presbyterian Hospital/Weill Cornell
> Medical Center.
>
> Dr. Kaplitt has devoted much of his academic
> research career to the development of effective
> gene therapy techniques against Parkinson's
> disease and other neurological disorders. In fact,
> 13 years ago, he and Dr. Matthew During pioneered
> a now widely used gene-delivery technique for the
> brain using an altered, harmless form of
> adeno-associated virus (AAV). In 2003, Dr. Kaplitt
> performed the world's first gene therapy surgery
> for Parkinson's, conducted at NewYork
> Presbyterian/Weill Cornell.
>
> "Viruses exist in nature mainly to transfer their
> own genes to the host cell," he explains. "So, we
> modify the AAV in such a way that the only gene it
> carries is the one we want to deliver to the
> therapeutic site."
>
> In this case, the "gene of interest" is the
> glutamic acid decarboxylase (GAD) gene. "GAD makes
> a chemical called GABA, a major inhibitory
> neurotransmitter in the brain that helps 'quiet'
> excessive neuronal firing," explains Dr. During,
> the senior author of the current study, who worked
> on this research while at Weill Cornell. Dr.
> During is now professor of molecular biology and
> cancer genetics at Ohio State University.
>
> "In Parkinson's disease, not only do patients lose
> many dopamine-producing brain cells, but they also
> develop substantial reductions in the activity and
> amount of GABA in their brains. This causes a
> dysfunction in brain circuitry responsible for
> coordinating movement," Dr. During explains.
>
> The researchers' bold idea: to insert the
> GABA-producing gene GAD back into an area of the
> brain called the subthalamic nucleus, a key
> regulatory center within this motor circuit.
>
> "Our hope was that with a single operation to this
> single site, we could boost GABA production and
> thereby normalize the function of the entire
> circuit," Dr. Kaplitt says. "Not only would this
> alter the chemical balance in the subthalamic
> nucleus; it should also provide GABA to other
> parts of the network that weren't getting enough
> of the neurotransmitter."
>
> To test that theory, the investigators injected
> the GAD-bearing AAV vector into the subthalamic
> nucleus of each of the 12 Parkinson's patients,
> but only on one side of their brains.
>
> "Because this was the first such study of its
> kind, we targeted just one side of the brain
> initially out of concerns for the patients'
> safety," Dr. During says. "However, since the
> patients were symptomatic on both sides of the
> brain, this also provided an untreated side for
> comparison with the treated hemisphere."
>
> The researchers then used a standard assessment of
> motor function, the Unified Parkinson's Disease
> Rating Scale (UPDRS) to track changes in patients'
> symptoms over the next 12 months. They also
> tracked changes in each patient's brain activity
> using positron emission tomography (PET) scans.
> These were both performed by the other two
> principal authors of the study, Drs. Andrew Feigin
> and David Eidelberg of North Shore-Long Island
> Jewish Health System.
>
> "Like all phase 1 studies, this one was primarily
> focused on gauging the safety of the technique,"
> Dr. Kaplitt says. "And on that count it succeeded
> brilliantly: We saw no adverse events related to
> the treatment, no immunological changes or
> infections over the year of the study, no imaging
> evidence of toxicity whatsoever."
>
> The results in terms of clinical and neurological
> efficacy were also encouraging.
>
> "In terms of the UPDRS scores measuring motor
> function, we observed significant improvements in
> the 'off-state' phase -- meaning that period when
> Parkinson's patients have been off their medicines
> for 12 hours -- and also in the on-medication
> phase, when they were taking their drugs," Dr.
> Kaplitt says.
>
> For example, at three months post-treatment, the
> patients as a group had already charted between a
> 25- and 30-percent improvement in off-state UPDRS
> scores, and those improvements persisted over the
> full year of the study. Similar results were seen
> in the on-medication state, the researchers found.
> Several individual patients showed impressive
> improvements of between 40 percent and 65
> percent.
>
> "That was really surprising and heartening,
> because traditional Parkinson's surgeries improve
> patients in the off-state but not as frequently in
> the on-medication state," Dr. Kaplitt says.
>
> "Interestingly, these improvements in motor
> function were due to the side of the body
> controlled by the brain hemisphere that had
> received the treatment," Dr. During notes. "Also,
> AAV tends to require several weeks to maximize and
> stabilize production of a therapeutic gene, and in
> fact we did not see significant clinical changes
> until more than 1 month after surgery. These both
> further suggest that it was the gene therapy that
> was driving their improvement."
>
> There were also strong trends toward reductions in
> medication-linked dyskinesia (movement
> difficulties) and improved activities of daily
> living, although neither of these trends reached
> statistical significance.
>
> Finally, PET scans revealed a more normal level of
> activity up to 1 year following surgery in exactly
> those areas of the brain that the researchers had
> been hoping to "fix." Again, this improvement
> "occurred only in that half of the brain that had
> received the GAD gene," Dr. Eidelberg says.
>
> Will these remarkable improvements persist" Only
> longer follow-up can tell, but prior studies in
> animals, including primates, suggest that the
> transplanted gene does stay active for years, Dr.
> Kaplitt says.
>
> "Our next step of course is to move towards a
> larger, more definitive efficacy-centered study,"
> he notes.
>
> "We believe that this breakthrough trial has
> implications that go far beyond Parkinson's
> research," Dr. Kaplitt adds. "It's taken us nearly
> two decades of hard work to get here, but the
> success of this trial lays the foundation for the
> use of gene therapy against neurological diseases
> generally. We've now shown that the genetic
> modification of the patient's own brain cells can
> be done safely, and it appears to have enough
> effectiveness in this case to justify further
> exploration -- potentially opening up gene therapy
> for a host of brain disorders."

Marsha or anyone else ; I have a couple of ?'s . Why do pPD not just eat food or take a supplement with glutamic acid . And does HD have a similar problem with glutamic acid ? Thank You . db

db, you don't want glutamic acid, what you want is more GABA. GABA helps to calm and get rid of excess glutamic acid. If you want more glutamate (glutamic acid), then eat foods with msg (smirk), but i guarantee you, you don't want this for hd. The memantine that i take is like GABA, it blocks the excess glutamate from excess neuro excitement, and thus prevents cell death. I don't really understand the following article fully myself, but some of it can be understood, it explains how glutamate is a neuro toxin:

[www.truthinlabeling.com]

PS These foods are also very high in natural glutamate: tomatoes, broccoli, mushrooms, soy sauce, and msg, which explains why i get severe migraines from broccoli and mushrooms lol hope this helps



Edited 1 time(s). Last edit at 08/15/2007 11:06PM by Barb.

Without knowing for sure I would guess that simply ingesting this either does not supply enough or it may not even cross the blood brain barrier. Even things that do cross the blood brain barrier may not target the areas of the brain where they are needed. That is part of the problem with BDNF and creatine. They do cross the blood brain barrier but we don't get to where it would do us the most good. That is why delivery systems may be more the key as opposed to some new compound. If we could get BDNF exactly where we wanted it, in the quantities we needed it to be, we might already have something with a curative effect. There may be bunches of effective compounds right now but we just can't sneak them in where we want them to go. That is why things that should do this or that don't do it in a curative manner.

Look at creatine. Naturally we get 2-4 grams a day. It looks like an additional 10 grams a day may have a positive effect. Now high dose trials looks like even more has a better effect. Some are taking up to 35 grams a day... to the point that they can tolerate it. But it still won't be a virtual cure as is. I am guessing that this is just a method of bull dogging into the brain. But what if it could be piggybacked there... disguised as something else that the brain accepts. Then it would target the areas we need it to be and also only need a fraction of the creatine needed now.

This is not HD exclusive research... so hopefully soon we will have some really cool delivery methods like AAV. I am betting that there are close cousins to this that we don't know about getting perfected. It would be ground breaking treatment and I am sure it's being worked on ...some in the open and some behind closed doors. It would drastically change our methodology for looking for treatments... and I assume speed up the time frame for something really effective being found. Marsha just wrote something similar a week or two ago...too lazy to search for it... Probably was a lot better too. The term "Trojan horse" will probably turn it up.

Thanks for the info. I am finding the more I study lately about HD , that I am starting to get muddled in my brain . I am not sure why , things are getting muddled , but muddled I am . db

This is the best answer we could have gotten. Although Parkinsons hasn't been proven to be totally genetic, the results by modifying the gene is amazing.

It would be interesting to see if anyone has or is developing this same technology for HD.

Either way, it's a breath of fresh air to find something with so much potential that ACTUALLY works!