Dopamine copy-cat to treat Parkinson’s mimic


A Saudi Arabian family was found to have a genetic mutation leading to symptoms similar to parkinson’s disease, but the normal tests for the disease indicated otherwise. Researchers of the University of Toronto found that using a dopamine agonist reversed this parkinsonian condition almost completely.

Of this family, eight children, with a 16 year old as the eldest, were found to have symptoms of brain dopamine-serotonin vesicular transport disease, a VMAT2 deficiency. VMAT2 is a transporter protein that escorts dopamine across the neuronal synapse to its receptor.

Dopamine, in this context, serves as a way for neurons to communicate signals to each other. This was the mechanism breaking down in these children. The children’s symptoms from not having this neurotransmitter transporter were slow walking, difficulty initiating movement, droopy eyelids, audible breathing, dystonia, and other dopamine deficiency signs.

Through analysis of single nucleotide polymorphisms (SNPs pronounces “snips”) a mutation of the SLC18A2 gene was found as the cause of the VMAT2 absence.

To treat, the children were given a compound that activates dopamine receptors, a dopamine agonist, in hopes of making up for the neurotransmitters not hitting their marks. The compound was pramipexole. In less than seven days, improvement was seen. The jerky movements, trouble walking, and accompanying symptoms were almost completely gone after treatment.

The dopamine agonist was shown to nearly reverse all symptoms of the congenital dopamine transporter disease. Dopamine has proven once again how essential it is to the living system.

Jennifer J. Rilstone, Reem A. Alkhater, Berge A. Minassian. Brain Dopamine–Serotonin Vesicular Transport Disease and Its Treatment. The New England Journal of Medicine, 2013.


Mutations for cancer begin before cancer

Cancer cells mid-division. Photo courtesy of The Telegraph

Cancer cells mid-division.
Photo courtesy of The Telegraph

Cancer can prove one of the nastiest diseases to crop up in one’s body due to it remaining hidden until it has already metastasized and spread around the system. A Baltimore/Boston collaboration of researchers set out to prove over half of the somatic mutations that make up a tumor are present before “tumor growth” of self-renewing tissues even starts.

Tumors form as the result of genetic mutations in which more cell replication and division happens than cell death. This causes the overgrowth of cells resulting in cancerous masses. Cancers aren’t caused by a single mutation, however. Many things must go wrong in cells before they get out of control. The basis of this study was to see how many passenger mutations (those that do not affect cell growth) actually occur before the tumor is initiated (by driver mutations) and whether or not this was affected by patient age.

To test, data was analyzed from The Cancer Genome Atlas and the International Cancer Genome Consortium of 676 patients with chronic lymphocytic lekemia (CLL), uterine corpus endometrioid carcinoma, colorectal cancer, or pancreatic cancer. The researchers first found that the total number of somatic mutations found in these cancers increased with patient age (at diagnosis) (P<0.01). The mutation to age correlation was independent of cancer stage.

The results further indicated that over 50% of passenger mutations developed before a single driver mutation in median aged patients. Using the regression data shown in the article, the number of somatic mutations at the earliest stage of cancer detection (after 25 years for colorectal, after 7 years for leukemia, and after 10 years for uterine) was estimated as 5.86, 33.3, and 50.2 in the different cancers. This suggested 68%, 57%, and 51% respectively of the somatic mutations happened before the tumors initiated.

Finally, the mutations rates were estimated, but did not deviate much from that of normal cells and bacteria.

The results from this study showing that the number of somatic mutations in a patient are age dependent and that a large number of these mutations appear before cancer growth begins are relevant for current genome-cancer studies. From this data, it may be possible to predict a cancer’s appearance before it even starts.

Catching cancer early is one of the most important keys to stopping it. This project is a step closer to faster cancer detection and elimination.

Cristian Tomasetti, Bert Vogelstein, Giovanni Parmigiani. Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation. PNAS, 2013.