25 Aug '11
Oleg Kouzbit, Online News Managing Editor
Scientists from Russia’s leading biotech research labs are making quiet but steady progress on finding effective therapies for neurodegenerative diseases, particularly the most widespread and debilitating of them all—Alzheimer’s sclerosis. With patents in hand or applied for, researchers are now moving into pre-clinical trials.
Today we’ll take a look at Moscow’s Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry and Engelhardt Institute of Molecular Biology. Collaborating with colleagues from across Russia and beyond, they are developing and fine-tuning methods of curbing, if not stopping, the loss of neurons that leads to a critical loss of brain function.
Alzheimer’s fact sheet
Alzheimer’s sclerosis is one of the deadliest enemies of the human nervous system. First observed and described in 1906 by German physician Aloysius Alzheimer, the disease causes a loss of brain function that gradually gets worse over time. It affects memory, thinking, and behavior. Once a disease of the elderly, Alzheimer’s has been getting ‘younger’ and onset may begin as early as age 40. It is also hereditary.
According to the World Health Organization (WHO), at least 26 million people are crippled with Alzheimer’s. There is further evidence that indicates that this number may quadruple within 40 years.
Amnesia, or a partial loss of memory, is typically the earliest symptom, exacerbated as the disease advances by aphasia (damage to cortical speech areas), apraxia (movement disorders) and agnosia (inability to recognize people and objects). As the impairments build up, they eventually lead to a complete loss of decision-making ability, paralysis, and death.
On the attack
Alzheimer’s targets nerve cells’ protein-coding genes. As they get mutated, neurons’ contact points—synapses—get affected by hydrophobic amyloid protein aggregates called peptides. Forming fibrillar bundles, the peptides mold the so-called amyloid plaques.
These plaques disrupt neural and synaptic impulse transmissions, ultimately triggering a special mechanism, which ‘tells’ the human organism to destroy these dysfunctional nerve cells and disable the functions those cells were responsible for.
The body tries to restore order by using cells from its own immune system to fight the formations of amyloid peptides. But the wholesale attack by these ‘rescue rangers’ also causes inflammatory diseases of the central nervous system—like encephalomeningitis—thus worsening the situation.
Despite considerable progress in molecular studies of Alzheimer’s pathogenesis, contemporary therapies can only slow down the advancement of the disease but not reverse it.
Nurturing a ‘friendly’ peptide
At its bio research labs in Moscow and the town of Pushchino outside the Russian capital, a team from the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry is looking for substances powerful enough to prevent the degradation of nerve cells and build-up of pathologic (hydrophobic) proteins.
Institute researchers have reportedly identified a ‘good peptide’ that protects nerve cells instead of killing them to help restore one’s memory.
Fifteen years ago the Institute located a special protein referred to as human leukemia differentiation factor (HLDF) and found out that a tiny fragment consisting of just six amino acids was responsible for governing the functionality of the entire protein.
Scientists eventually concluded that this fragment—a new peptide, designated HLDF-6—improves long-term memory and possesses neuroprotective properties, positively affecting not only Alzheimer’s but Parkinson and cerebral infarction patients as well.
Researchers believe that HDLF-6’s therapeutic action is a result of genes responsible for biosynthesis enzymes and steroid hormone metabolism, which the new peptide activates.
What is still not clear is how the ‘friendly’ peptide actually works.
The HLDF-6 project has already been patented in Russia and pre-clinical trials are reportedly under way. The developers feel that if a full pre-clinical cycle is successful they will be able to do clinical trials in two years.
Looking into ‘heat shock’ protein
At another think-tank, the Russian Academy of Sciences’ Engelhardt Institute of Molecular Biology, scientists are studying the way the human’s main ‘stress’ or ‘heat shock’ protein, HSP70, releases its protective properties to counter Alzheimer’s.
The Institute is reportedly collaborating with colleagues from the University of New York and Russia’s Institute of Cell Biophysics.
The researchers have applied genetic engineering to obtain and purify an HSP70 specimen. Tests on animals have led to a decisive conclusion that used intra-nasally, the protein accumulates exactly in the brain areas that are most affected by Alzheimer’s.
One such area is the hippocampus—part of the human brain responsible for the consolidation of information from short-term memory to long-term memory and spatial navigation. It is one of the first in the body to suffer from Alzheimer’s.
A series of experiments has provided crucial evidence that the newly-developed specimen effectively stops an increase in amyloid protein levels and prevents degradation of the neuron structure and memory dysfunctions to help maintain a person’s cognitive ability.
According to portal Russia’s Science and Technology, the international research team applied for a Russo-American patent this past July.
The long-term goal of the project includes pre-clinical and clinical trials and production of enough protein to create a commercial medical product. Although the widespread use of intranasal HSP70-based therapy to treat neurodegenerative diseases is years away, the quiet but steady progress being made by both of these Russian institutes is attracting attention.