Huntington's Disease (HD) is a genetic disorder that leads to dementia and has been a complex task for pharma companies to try and conquer. As the battle rages on, a new drug by Pfizer has failed in phase three trials as reported by the medical giant this week.

The Hereditary Disease Foundation, a research group born out of the first support organization, was instrumental in finding the gene in 1993. Since that time there have been important discoveries every few years and understanding of the disease is improving in spite of a lack of sufficient treatment.

Current research directions include determining the exact mechanism of the disease, improving animal models to expedite research, clinical trials of pharmaceuticals to treat symptoms or slow the progression of the disease, and studying procedures such as stem cell therapy with the goal of repairing damage caused by the disease.

David Hung, M.D., president and chief executive officer of Medivation, that was in a joint effort with Pfizer stated:

"We are disappointed with the results of the HORIZON trial given the high unmet need in this patient population. At this point, we will discontinue development of dimebon in Huntington disease, including the ongoing open-label extension study. We will continue our ongoing 12-month Phase 3 CONCERT trial of dimebon and its open-label extension in patients with mild-to-moderate Alzheimer's disease. We expect to report top-line data from CONCERT in the first half of 2012."

Medivation and Pfizer have a global collaboration to develop and commercialize dimebon for the treatment of Alzheimer's disease and Huntington disease. Under the terms of the agreement, the companies work together on the dimebon development program.

All homo sapiens have the Huntingtin gene (HTT), which codes for the protein Huntingtin (Htt). Part of this gene is a repeated section called a trinucleotide repeat, which varies in length between individuals and may change length between generations.

According to Medilexicon.com:

"Huntington's Disease is a neurodegenerative disorder, with onset usually in the third or fourth decade, characterized by chorea and dementia; pathologically, there is bilateral marked atrophy of the putamen and the head of the caudate nucleus. Autosomal dominant inheritance with complete penetrance, caused by mutation associated with trinucleotide repeat expansion in the Huntington gene (HD) on chromosome 4p."

When the length of this repeated section reaches a certain threshold, it produces an altered form of the protein, called mutant Huntingtin protein (mHtt). The differing functions of these proteins are the cause of pathological changes which in turn cause the disease symptoms. The Huntington's disease mutation is genetically dominant and almost fully penetrant: mutation of either of a person's HTT genes causes the disease.

It is not inherited according to sex, but the length of the repeated section of the gene, and hence its severity, can be influenced by the sex of the affected parent.

Pfizer's Steve Romano, M.D., senior vice president, Medicines Development Group head, Primary Care Business Unit adds:

"Huntington's is a challenging disease area, and we are also disappointed with the HORIZON results. The results are expected to be presented at an upcoming medical meeting."

The search for a solution will continue according to researchers.

Sources: The Lancet and Medivation News Release

Written by Sy Kraft