As reported here on the biOasis blog, there has been enormously encouraging news on the Alzheimer’s research front. The research uncovered three new gene variants associated with Alzheimer’s Disease. Encouraging as the find may be, this is really just proof for something that was thought all along: that there is a hereditary component to Alzheimer’s Disease. Now researchers are closer to learning where that hereditary component is located and where to target possible medication, as well as achieve diagnosis.
A less-than-encouraging element to this research is that it regards late stage Alzheimer’s, rather than early-onset Alzheimer’s. As reported in the Washington Post,
This story refers to the common (that is, late-onset) form of Alzheimer’s disease. Other established mutations related to Alzheimer’s have been for the risk of the rare early-onset form. Other reports of genetic links to Alzheimer’s risk have not been replicated. As the researchers state in their paper: “More than 550 other genes have been proposed as candidates for Alzheimer’s disease susceptibility, but thus far none have been confirmed to have a role in Alzheimer’s disease pathogenesis.
So it is a step forward, but hardly definitive, especially as it applies to early diagnosis and treatment. Not to diminish the outstanding progress inherent in this new study, but there is still much work to be done. The main findings of the research are as follows:
A previously identified Alzheimer’s gene known to promote the overproduction of amyloid proteins that collect outside neurons was confirmed by the research, while two of the new genes identified were found to play a role in determining the ability of the brain to rid itself of these toxic proteins. The new findings indicate that both the production and removal of these complex proteins are associated with Alzheimer’s disease.
What is significant about this is that there has been recent research refuting that amyloid plaque is the determining factor in Alzheimer’s Disease. The amyloid plaque hypothesis (building up in plaque causes AD) is conventional wisdom, and so most drug research is targeted in this area. Troubling – though interesting – additional research has suggested that the exact opposite may actually be the case, which could mean much research into new drug therapy has the wrong emphasis. From Newsweek:
“I would say that conventional wisdom in the field . . . is that an amyloid benefit would mean amyloid-lowering,” Gandy told me by e-mail from Vienna. “Certainly, up until now, no one has been looking (intentionally) to treat Alzheimer’s by raising amyloid levels. [So] it was startling to observe that a compound with an apparently beneficial clinical effect on cognition caused acute elevation of amyloid beta levels in 3 out of 3 systems, in 2 labs.”
This hypothesis turns conventional Alzheimer’s drug research on its head. What is interesting about the new research into the genes associated with AD is the research potentially refutes these claims about amyloid plaque. To repeat: “The new findings indicate that both the production and removal of these complex proteins are associated with Alzheimer’s disease.”
That said, the argument could effectively be made that this does not throw the amyloid hypothesis out the window. The new research merely confirms that the production of amyloid is integral to the progression of Alzheimer’s Disease. This was already understood, but now we’re one step closer to possibly having a definitive answer about the amyloid hypothesis and devising effective drug treatment that can target amyloid plaque in the most effective method possible.
Gene Therapy and the Blood Brain Barrier
There has been some research into gene therapy for Alzheimer’s Disease, but with the common result: more research is needed. However, recent gene research is NOT to be confused with gene therapy. What is particularly problematic about gene therapy is that it may require brain surgery:
Earlier studies working with Nerve Growth Factor (NGF) had shown that injecting NGF-producing tissue into the brains of aging monkeys could reverse deterioration. Simply injecting NGF into people would not work. If it goes into the wrong part of the brain, it can cause serious side effects.
So, doctors drilled holes into the patients’ skulls and implanted the NGF-producing skin cells directly onto Alzheimer’s-injured spots.
This is hardly feasible for the 5 million plus people who suffer from the disease – a number that is certainly to grow – and it certainlyly poses an increased risk for side effects. There is more research currently being done in this area, but nothing definitive has been established regarding this process.
It is possible to have a pharmaceutical solution that “rebuilds” the brain in much the same way as current gene therapy, but with a less-invasive procedure – and that treatment may evolve out of the research into what genes cause Alzheimer’s Disease. A pharmaceutical treatment that can be transported into the brain seems more sensible an approach than injecting a solution into the brain with a complicated and likely-costly process.
This is what makes the blood brain barrier so vital to Alzheimer’s research. Instead of injecting a solution into the brain by an invasive technique, a pharmaceutical drug that is able to cross the threshold of the blood brain barrier could have the same effect – no surgery involved. BiOasis’s research into p97 is aimed at improving the brain’s capabilities without the need for surgery. Clinical trials into gene therapy and research into the genetic basis of Alzheimer’s Disease will play a significant part in how p97 can revolutionize Alzheimer’s treatment. When it is determined the best approach to halt Alzheimer’s, p97 can deliver treatment across the BBB effectively and safely.
