sedative claimed worldwide infamy for causing horrible birth defects in a generation of European and Canadian children, Thalidomide continues to stir dread and regret in society’s collective conscience. The iconic black-and-white photos of its young victims, many born with missing and malformed limbs, remain as chilling as ever.
However, in the late ’90s, the once-maligned drug experienced a reprieve of sorts when it was found to effectively treat the bone cancer multiple myeloma, with subsequent studies showing its efficacy combating other cancers. Now, Valley neurologist Marwan Sabbagh, director of the Banner Sun Health Research Institute in Sun City, is hoping to rebrand Thalidomide as a potential miracle drug for another crippling disease: Alzheimer’s.
He got the idea after reading a 2006 pilot study that demonstrated the arthritis drug Enbrel (Etanercept) could potentially be effective in treating Alzheimer’s. It did so by blocking the inflammation marker TNF-Alpha, which Banner scientists had previously identified as a major actor in the production of BACE, the key enzyme responsible for the amyloid plaque that degrades the brain’s neurons and causes Alzheimer’s symptoms.
“Thalidomide does the same thing as Etanercept. That’s been well known for a long time, so we thought, ‘Let’s check it out,’” recalls Sabbagh, who started testing the drug on groups of mice in 2008 and discovered a 50-percent reduction in amyloid in those treated. “We found it not only blocked TNF-Alpha and BACE [which Etanercept doesn’t inhibit] but it blocked amyloid production and there was less amyloid in their brains. It was a very robust effect.”
However, brain researchers have yet to find consensus on the best methodology to fight Alzheimer’s via amyloid-inhibiting drugs. “The discussions have centered around: Do you clear out the amyloid you have or block the production you’re making?” Sabbagh explains. “Nobody’s agreed on that.”
In other words, whether or not researchers find the magic amyloid threshold that triggers dementia, how to best manage that threshold – proactively or retroactively – will be the key to unlocking the secrets of this mysterious disease. In the meantime, researchers agree on the need to develop drugs that tackle Alzheimer’s from both offensive and defensive sides of the field. Sabbagh thinks treatment of Alzheimer’s will ultimately mimic that of cancer, with no single panacea, but multiple agents such as Thalidomide working in tandem via drug cocktails.
By identifying a potentially effective agent in Thalidomide, Sabbagh and his team scored a $900,000 grant from the National Institutes of Health in 2009 to explore their findings over a two-year period. Currently, Banner is holding a Phase II human clinical trial with a pill form of Thalidomide – checking progress via blood samples and elective spinal tap. The trials are currently half-full and seeking applicants in the mild-to-moderate stages of the disease.
“It’s not well-tolerated in elderly people,” admits Sabbagh, noting sedation and constipation are two side effects of the drug. Though none of the eight patients to complete the trial have been able to tolerate the 400 milligram maximum dosage, Sabbagh is hopeful that the trial outcomes, still undisclosed, will yield positive results and lead to a multi-center Phase III trial (the last trial before FDA drug approval) by the end of 2013.
One iron-clad prerequisite for trial volunteers: None of them can come into contact with pregnant women.
“The irony is that, for better or worse, we know everything about Thalidomide we need to know,” Sabbagh says. “Typically when you do trials with newly developed drugs, you have no idea what you’re dealing with – if it’s going to be good, if it’s going to be a disaster, if it’s going to kill people – so the advantage of Thalidomide is that it’s a known quantity. We know the safety, and we know the risk, so we can focus our energies.”
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