Neurotrophic growth factors such as FGF show tremendous promise as a treatment to protect neurons in Huntington's disease as shown in a 2005 review by Dr. LaVonne Goodman. [HDL: Neurotrophins to the Rescue]
ENKAM has done a tremendous amount of research on NCAMs and on their mimetic version, all of which is new to me. The mechanism of interest for HD research is that NCAMs are FGF receptor agonists and contribute to neuroprotection. But NCAMs also do some other intesting things. As their name suggests, they allow neurons to connect to each other. They also play an important role in the development and migration of neurons as well as in the formation and consolidation of memory. It seems possible that cognition could be also be improved in HD patients with the use of ENKAM's synthetic peptide which mimics NCAM.
As an interesting aside, a google search turned up a new study which looked at evolutionary differences between humans and chimpanzees, with which we share more than 98 percent of our genes. The study found that genes relating to cells adhesion molecules are a major difference. The authors suggest that NCAMS may play a critical role in our humanity. This makes sense given the importance of long term memory in cognition. [Research News: Neuron Cell Stickiness May Hold Key to Evolution of the Human Brain].
A huge issue in developing treatments for neurodegenerative disorders such as HD or Parkinson's disease is delivery. Because of the blood brain barrier, some potential treatments would require surgical intrusion and the placement and replacement of slow release capsules. ENKAM's technology is exciting because its compounds can be administered either nasally or through injection.
A timeline shown on the ENKAM website shows a plan to start Phase I clinical trials toward the end of 2007, assuming of course that the preclinical (animal) studies go well.
Cambon K, Hansen SM, Venero C, Herrero AI, Skibo G, Berezin V, Bock E, Sandi C. A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation. J Neurosci 2004;24:4197-4204.
Klementiev B, Novikova T, Penkowa M, Berezin V, Bock E. A synthetic NCAM mimetic peptide, P2, facilitates recovery of cognitive and motor functions after traumatic brain injury. J.Neurol. 2006;253:II/90.
Neiiendam JL, Kohler LB, Christensen C, Li S, Pedersen MV, Ditlevsen DK, Kornum MK, Kiselyov VV, Berezin V, Bock E. An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons. J Neurochem 2004;91:920-935.
Prabhakar S, Noonan J, Paabo S, Rubin E. Accelerated Evolution of Conserved Noncoding Sequences in Humans. Science 2006;314:786.
Welzl H, Stork O. Cell Adhesion Molecules: Key Players in Memory Consolidation? News in Physiological Sciences 2003;18:147-150.
CHDI, Inc. (CHDI), a non-profit organisation, together with ENKAM Pharmaceuticals A/S, the Copenhagen-based biotechnology company focused on cancer and neurodegenerative diseases, are pleased to announce that they have entered into a collaboration to test two of ENKAM’s preclinical compounds in the area of Huntington’s disease (HD). CHDI will provide pre-clinical development resources.
Commenting on the announcement, Robert Pacifici, Chief Scientific Officer of CHDI, said: “ENKAM’s approach to developing trophic factor mimetics may be very useful in developing therapies for HD. We look forward to joining forces with ENKAM to explore the potential utility of their candidate molecules in relevant animal models of HD”.
CHDI will pay for the preclinical testing of two of ENKAMs compounds, both of which target the FGF-receptor. One of the compounds is derived from the Neural Cell Adhesion Molecule (NCAM) and the other is derived from the fibroblast growth factor (FGF). ENKAM will retain all rights to the products.
The scientific foundation of ENKAM is built upon decades of research in cell adhesion, growth and differentiation leading to our understanding of the regulatory role of cell adhesion molecules (CAMs) over associated growth factor receptors. CAMs are known to play a significant role in the development of tissues and organs. In recent years, increasing evidence of a direct regulatory role of CAMs over growth factors has been published. This valuable but complex group of targets has been made accessible by dissecting the three-dimensional structure of complex interaction between receptors and their ligands into sub-binding sites and targeting those sub-binding sites with peptides.
Professor Elisabeth Bock, a co-founder of ENKAM, said:“We are delighted that CHDI and High Q have selected our compounds for development. This is a huge endorsement of our science and our capability to develop ENKAM’s compounds into therapies for severe neurodegenerative disorders, such as Huntington’s disease.”
Adding to this comment, Morten Albrechtsen MD, Chief Executive and a co-founder of ENKAM Pharmaceuticals, said:“We are delighted to work together with CHDI and High Q to advance therapies for treatment of Huntington’s disease.”