Saturday, June 23, 2018

Eteplirsen for Duchenne Muscular Dystrophy

Eteplirsen is a new drug for treatment of Duchenne muscular dystrophy.  Its brand name is Exondys 51.  Eteplirsen is an antisense morpholino.

Duchenne muscular dystrophy occurs from a mutation of the gene for dystrophin.  Usually this is a deletion of part of the gene.  The dystrophin protein protein reinforces the muscle cell membrane and acts like he wooden frame of the walls of a house.  As muscle cells contract and lengthen during movement, dystrophin reinforces the cell membrane and protects it from damage. Boys and men who have Duchenne muscular dystrophy have no dystrophin or almost no dystrophin in their muscles.  Even a very small amount of dystrophin helps a lot.  This is why males who have Becker muscular dystrophy, and have a reduced amount of function dystrophy have a milder disease that those who have Duchenne muscular dystrophy and have almost none.

The deletion in the gene for dystrophin disrupts the reading frame when the internal cell mechanisms read the gene to make dystrophin.  Every part of the gene past the deletion codes wrong the gene product is no good.  The antisense morpholino results in skipping over the part the gene that is disrupted.  The cell reads the gene correctly before and after the skipped portion. The gene product is a dystrophin molecule that is missing a piece in the middle but is otherwise normal and functional.

About 13 % of boys who have Duchenne muscular  dystrophy have deletion that Exondys 51 can treat.  Antisense morpholinos for other gene deletions are in development.

Further Reading

Annals of Neurology 2016 Paper: Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy
Abstract with link to free full text article

Neurology 2018 Paper: Eteplirsen treatment for Duchenne muscular dystrophy: Exon skipping and dystrophin production

Muscular Dystrophy Association
Search the MDA website for news and information

Sarepta (the pharmaceutical company that makes Exondys 51)
Search the Sarepta website for news and more information

Wikipedia article on morpholinos

Saturday, May 19, 2018

Theracurmin Improves Cognition and Reduces Amyloid Beta

A recent study published in the American Journal of Geriatric Psychiatry showed that taking Theracurmin, a bioavailable form of curcumin, improved memory and other measures in non-demented persons compared to controls, and seemed to prevent accumulation of amyloid beta and tau protein, as measured using FDDNP (TauMark) PET scans.  Amyloid beta and tau are important biomarkers in the brain for Alzheimer's disease.  Prevention or reduction in the accumulation of amyloid beta and tau protein might mean that Theracurmin prevents or delays the onset of Alzheimer's disease, but further studies are needed to see if this is true.

Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial.

Am J Geriatr Psychiatry. 2018 Mar;26(3):266-277. doi: 10.1016/j.jagp.2017.10.010. Epub 2017 Oct 27.

Friday, May 18, 2018

Mediterranean diet and lifestyle may reduce the risk of Alzheimer's disease

A new study published in the May 15 issue of the journal Neurology showed that 30- to 60-year-old cognitively normal persons who adhered to a Mediterranean diet developed less markers for Alzheimer's disease pathology and PET scans than those who did not.  People who did not adhere to this diet had more beta amyloid and lower glucose metabolism in brain regions most affected by Alzheimer's disease.  These PET scan findings are biomarkers that correlate strongly with development of Alzheimer's disease.

Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults

Another study done in New York found that following a Mediterranean diet reduced the risk of onset of Alzheimer's disease.

Mediterranean diet and risk for Alzheimer's disease

Another study found that modification of 7 risk factors may greatly reduce the risk of developing Alzheimer's disease.

The projected effect of risk factor reduction on Alzheimer's disease prevalence

These modifiable risk factors included diabetes, midlife hypertension, midlife obesity, smoking, depression, cognitive inactivity or low educational attainment, and physical inactivity. 

Another study published in the April 10 issue of Neurology found that high cardiovascular fitness in a large cohort of Swedish women delayed the onset of dementia.

Midlife cardiovascular fitness and dementiaA 44-year longitudinal population study in women

What these studies show its that living a healthy lifestyle can delay the onset of dementia.