The Tangled Neuron

Update on Axona

Summary:   Results of a clinical trial of Axona show the medical food may be an effective treatment for people with mild to moderate Alzheimer’s, at least for those who don’t have the APOE4 genetic variation.   Accera is planning a larger trial to confirm these results.

The company is also planning an imaging study to try to prove that treatment with Axona changes the metabolism of certain areas of the brain, and that those changes are linked with improvements in cognition.    If successful, Accera could be among the first to show that changes to a “biomarker” reflect real changes in memory and thinking.

I’ve written before about Accera’s Axona, a medical food available by prescription for people diagnosed with mild to moderate Alzheimer’s.  The theory behind Axona is that if brain cells aren’t getting or using enough glucose, you can substitute ketone bodies for glucose.  A ketone body is a substance created when fats are broken down in the body.  Axona increases the level of ketone bodies in the blood, and in theory, provides an alternate fuel for brain cells.

Last week, I talked with Steve Orndorff, President and CEO of Accera, to get an update on his company’s product.  Data from an initial trial of Axona have now been published, and the results are encouraging enough for Accera to plan a larger clinical trial, he says.

Early AD Symposium: John Morris Makes the Case for "Preclinical Alzheimer's Disease"

            John Morris, MD

Dr. John Morris is a Professor at Washington University in St. Louis and Director of the Alzheimer’s Disease Research Center  there.  One of his areas of interest is detecting “preclinical Alzheimer’s disease.”  He made the case for this relatively new concept in the first day’s keynote address at the Symposium on Early Alzheimer’s Disease in Miami Beach earlier this month.

Alzheimer’s should be viewed more as a chronic disease, he said, and this concept includes a “preclinical” phase where there are changes in the brain, but no noticeable symptoms.  Despite some studies showing people with large amounts of Alzheimer’s pathology (plaques and tangles) can have normal memory and thinking, he does not believe that pathology is harmless.  He and his colleagues have shown that people with Alzheimer’s pathology who seem cognitively normal already have brain shrinkage in some areas.  Tests show that their memory and thinking has already declined over time.  They will develop dementia if they live long enough, he thinks.

The Father of the MMSE

Marshal Folstein, MD

Marshal Folstein, who along with his wife Susan, developed the Mini-Mental State Examination (MMSE) used to screen for cognitive impairment was at the Symposium on Early Alzheimer’s Disease in Miami Beach this year.

New Data on Axona

Acerra says it is presenting data at the Alzheimer's Disease International conference that shows Axona helps memory and thinking, at least in people without the APOE4 genetic variation who take Axona as prescribed. I'll work to get some details on this data.

Amyloid in Alzheimer’s: Part of the Immune System?

Summary:  A new report from researchers at Massachusetts General Hospital suggests that the beta amyloid protein that makes up Alzheimer’s plaques might be part of a normal immune response.   If confirmed, this could explain how and why infection, brain injury, stroke and anesthesia are linked to increased risk of dementia.  This new model of how Alzheimer’s develops could also suggest new ways to prevent abnormal buildup of beta amyloid and treat or prevent dementia.

Researchers at Massachusetts General Hospital and their colleagues have reported that the beta amyloid protein that makes up Alzheimer’s plaques can reduce the growth of several  types of  bacteria and a yeast, all of which cause infections in the brain.

Bapineuzumab May Reduce Plaques, But Does it Treat Alzheimer’s?

Elan reported last week that its Phase II study of bapineuzumab in 28 Alzheimer’s patients showed that the potential drug reduced a type of beta amyloid (the protein that makes up Alzheimer’s plaques) in the brains of the patients receiving treatment.  This reduction was seen with PET scans using the PiB compound. 

The study is interesting because PiB imaging is a non-invasive way for researchers to measure the amount of amyloid in the brain, and it did show that the treatment reduced amyloid.

But it’s hard to say whether this means bapineuzumab might actually treat dementia.  A previous Phase II clinical trial of the potential drug in 234 patients did not show a difference between those receiving treatment and those receiving a placebo, perhaps because of issues with trial design.  We’ll have to wait a couple of years for the results of the Phase III trial to see whether bapineuzumab can improve memory and thinking.

If the drug reduces amyloid in the brain, but doesn’t affect symptoms, we’re bound to hear a lot of questions about the strategy of reducing amyloid to prevent or treat dementia. 

Note:  Elan has sold the rights to bapineuzumab to Janssen Alzheimer Immunotherapy, but now owns part of that company.

Dimebon Fails in Clinical Trials

Pfizer and its partner Medivation have announced the failure of Dimebon in Phase 3 clinical trials.  This news, just the latest of several failures, will give more weight to the idea of pushing the reset button for Alzheimer's research.

The Thousand Mile Stare: A Conversation with Gary Reiswig

My friend Chuck Jackson was diagnosed with young onset Alzheimer’s disease at age 50.  It wasn’t a total surprise to him – his brother was being treated for Alzheimer’s and many of his cousins had it.  His mother and at least nine of her siblings had it.  Most had symptoms early in midlife; some died while still in their 50s.  Chuck and many of his relatives have a rare genetic variation called presenilin 2, or PS2, that almost guarantees a person will develop Alzheimer’s.

It’s only recently that the stigma attached to dementia has lessened.  For a long time, Chuck’s relatives didn’t talk much about their family history.  But since his diagnosis in 2004, Chuck has talked with support groups, participated in research and testified before Congress.
 
His cousin Gary Reiswig, who now knows he does not carry the PS2 gene variation, has gone even more public about the disease that has ravaged his family.  His new book, The Thousand Mile Stare: One Family's Journey through the Science and Struggle of Alzheimer's, is a very personal journey through generations of disease and tragedy.

The book opens in 1936, when Gary and Chuck’s grandfather, perhaps in the early stages of Alzheimer’s, drove his truck into the path of an oncoming train in rural Oklahoma.  He and one of his sons were injured, and his wife was killed.  From that story, so emblematic of the family’s problems, the book spans two continents and more than two hundred years.  The family’s roots as “Volga Germans” who left Germany to farm land along the Volga River in Russia in the 1700s are interesting, but it’s the little details of daily life with Alzheimer’s that make this book so riveting.