New study showed that daily corticosteroid therapy was superior to alternating therapy for boys who have Duchenne Muscular Dystrophy

 Effect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys With Duchenne Muscular Dystrophy

A Randomized Clinical Trial

JAMA. 2022;327(15):1456-1468. doi:10.1001/jama.2022.4315
Published online April 5, 2022.

This clinical trial compared 3 corticosteroid treatment regimens for boys who had Duchenne muscular dystrophy:

• Prednisone 0.75 mg per kg body weight daily
• Deflazacort (Emflaza) 0.9 mg per kg body weight daily
• Prednisone 0.75 mg per kg body weight for 10 days alternating with 10 days of no prednisone

After 3 years the investigators found that the boys who took either daily regimen did better than the boys who took prednisone on an alternating regimen of 10 days on and 10 days off.  Side effects were similar among the groups.  The outcomes of the two daily corticosteroid regimens were not significantly different.

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
Abstract

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

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.

https://www.ncbi.nlm.nih.gov/m/pubmed/29246725/?i=2&from=theracurmin#fft

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

https://www.ncbi.nlm.nih.gov/pubmed/29653991/?ncbi_mmode=std

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

https://www.ncbi.nlm.nih.gov/pubmed/16622828?access_num=16622828&link_type=MED&dopt=Abstract

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

https://www.ncbi.nlm.nih.gov/pubmed/21775213?access_num=21775213&link_type=MED&dopt=Abstract

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

http://n.neurology.org/content/neurology/90/15/e1298.full.pdf

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

Substance Abuse and Stroke

            Many commonly abused drugs can cause strokes.  The only way to avoid this risk is by not taking them.

OPIATES      

Opiates are narcotics. Their risk of causing stroke occurs mostly with intravenous use.  They include heroin, morphine, Demerol (meperidine), and Dilaudid (hydromorphone).  When oral narcotics are ground up and injected the risk is increased due to small solid particles that are injected.

Endocarditis

Intravenous injection of drugs can cause bacteria to be injected along with the drug.  This can cause endocarditis, an infection inside the heart.  Infected blood clots form and break off as emboli, which are pieces of clots floating in the bloodstream.  These can travel to arteries in the brain and block them.  The clots can cause ischemic stroke when the brain tissue has no blood and is killed.  The clots can also cause hemorrhagic stroke when the arteries damaged by the clots break open and bleed into the brain.  Because these clots are infected they can cause brain abscesses, which are infections that cause cavities with collections of pus in the brain.

Liver and Kidney Damage

Heroin users may have hemorrhagic strokes if they develop hepatitis (such as hepatitis B from the injection with a needle that has hepatitis virus in it), liver failure and loss of blood clotting factors made by the liver. They may hemorrhagic strokes if they develop heroin nephropathy in which the heroin damages the kidneys causing uremia (kidney failure) or high blood pressure from kidney damage.

Vasculitis

This is an inflammation of larger arteries that can be caused by intravenous drug use. The arteries become blocked by the inflammation and the blood flow is cut off.

Diffuse angiitis

This is an inflammation of the smaller arteries.

Emboli from Particles

Emboli from talc or adulterants of injected drugs: Particles of talc, other contaminants, or undissolved particles from tablets that are ground up to inject can act like blood clots and block arteries and cause strokes.

AMPHETAMINE AND RELATED AGENTS

Acute intoxication

Acute drug intoxication causes excitement, high blood pressure, fever, coma, vascular collapse (failure of the circulatory system), and death.

Necrotizing Angiitis

This is associated with methamphetamine, usually intravenous.  It is an inflammation of the wall of arteries and can cause scarring and obstruction of the artery. It also can cause necrosis of the artery. The tissue of the arterial wall dies and the artery breaks open.  This can result in ischemic stroke (blocked arteries and death of brain tissue) or hemorrhagic stroke (bleeding into the brain).  Arteries can affected anywhere in the body.

COCAINE

Cocaine may cause ischemic or hemorrhagic stroke.  It can cause vasospasm (spasm of the arteries) or vasculitis (inflammation of the arteries).  Cocaine can cause the same problems in the coronary arteries (the arteries that supply blood to the heart muscle) and can cause a heart attack.  Ingestion of alcohol with cocaine results in metabolism (conversion) of cocaine to cocaethylene, which is more potent than cocaine.  Cocaine use during pregnancy may cause neonatal stroke (stroke in the newborn baby) and possibly brain malformations.

PHENCYCLIDINE (PCP)

PCP causes high blood pressure both early and late after ingestion.  PCP causes constriction of blood vessels in the brain.  Because PCP is stored in fat, people have recurring episodes of PCP intoxication when it is release from the fat.

LSD

LSD causes hypertension and vasospasm.  Vascular occlusion (blocked arteries) and stroke have been reported to occur.

MARIJUANA

Delta-9-tetrahydrocannabinol is the active ingredient of marijuana.  It has a vasoconstrictor effect in animal studies.  Proposed mechanisms for causing stroke include cerebral vasospasm (spasm of arteries in the brain). Marijuana is also associated with widespread narrowing of arteries in the brain.

INHALANTS

Sniffing glue or toluene may cause stroke, vasospasm (constriction of arteries), or cardiac arrhythmia (an irregular heart rhythm that can cause a blood clot leading to a stroke).

References

CONTINUUM.  Acute Stroke Management.  Volume 9.  Number 2.  April, 2003.

Mohr JP, Choi DW, Grotta JC, Weir B, Wolf PA.  Stroke: Pathophysiology, Diagnosis, and Management.  4^th Ed.  Churchill Livingstone, 2004.

Copyright 2012 Neurology Associates of Arlington, P.A.

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