New Hope for Thalassemia Sufferers

The blood disorder, Thalassemia is very prevalent among the Kadazandusuns.

Last month I donated blood in support of a 30+ year old thalassemic girl who lives just 3 houses next to mine. She has had blood transfusions since small but since she had bone marrow transplant she had the joy of enjoying her thirties age. Hopefully she will enjoy many more, especially at this time when the promise of new technologies offers brighter hopes for a better cure.

In a 2008 study headed by a researcher from the Faculty of Medicine, University of Malaya, from 125 blood samples obtained from unrelated Kadazandusuns, α- and β-thalassemia were confirmed at 33.6% and 12.8%. In another study it was found that from all the ethnic groups studied in Sabah, Kadazandusuns showed the highest prevalence for this disease.

Thalassemia is an inherited blood disorder in which the body makes an abnormal form of hemoglobin, the protein molecule found in red blood cells. The disorder results in excessive destruction of red blood cells, which leads to anemia. It is caused by either a genetic mutation or a deletion of certain key gene fragments. There are two main forms of thalassemia which are serious: In alpha thalassemia, at least one of the alpha globin genes has a mutation or abnormality, and in beta thalassemia, the beta globin genes are affected.

People with thalassemia can get sick from an overload of iron in their bodies, either from the disease itself or from frequent blood transfusions. Young children, even with blood transfusions, are not expected to reach beyond their teen years because of this disease. Bone marrow transplantation—or in more detail, the blood-making stem cells (hematopoietic stem cells) found in bone marrow, but more of this later)?—may offer the only possibility (so far) of a cure in young people who have an HLA-matched donor. Success rates have been in the 80–90% range.

If you recalled, the root cause of thalassemia is the inability of the body to make either one of two proteins that makes haemoglobin, and that deficiency arose because the sufferer’s crucial deletion or mutation in his/her genome (genes that codes for the making of the protein(s). But, what if somehow those missing/bad genes can be corrected? What if it is possible, much like a software programmer can edit his code, to shift though the 3 billion plus of DNA code pairs in the human genome, zero in on the flawed part, delete it, and replace with the right and healthy one?

Enter CRISPR (Clustered regularly interspaced short palindromic repeats) technology, a new method of targeted gene modification discovered not more than 5 years ago. More specifically known as CRISPR/Cas9, this technology makes it possible to do genome editing – the precise and targeted modification of the genetic material of cells. Genome editing works by using an enzyme to make a cut at a particular sequence in the genome, followed by the deletion, repair or insertion of genetic material at the cut site.

Can CRISPR genome editing pave the way for a better and safer cure for thalassemia? Sci-fi wishful thinking? Think again.

Today (2nd August in the U.S.), it was reported in the Washington Post that scientists have successfully undertaken gene editing in the first human embryo CRISPR experiment in U.S. to corrects gene for an inherited heart disease, hypertrophic cardiomyopathy. This method of genome editing and repair has already been found to work in a mouse with the β-thalassemia defective gene, with “sustained elevation of blood haemoglobin levels into the normal range, reduced reticulocytosis, [and] reversal of splenomegaly “. In 2015 a team of Chinese scientists, using the same technology, reported that their success rate was one in four for β-thalassemia genetically abnormal human embryos although they did raised their concerns about off-target effects. Just last march, Intellia Therapuetics, a company dedicated to developing potentially curative genome editing treatments, together with healthcare global giant, Novartis, have announced that their hematopoietic stem cell transplant (read “thalassemia” here) program is planned to undertake the first human clinical study next year. A different company, CRISPR Therapeutic is also targeting human clinical trials for β-thalassemia treatments with about the same timeline.

Here’s praying for my neighbour. And for my cousin-in-law, who is a carrier of the thalassemia gene.

Curry Lamb

Last night in preparing the Coconut Battered Ikan Bakulan I saved the santan. Instead of throwing the perfectly good natural organic santan (yeah, much better than the supermarket package kind) I used it to cook lamb curry, yeah :-). Nothing special here – I mixed 2/3 kari daging with 1/3 curry ikan. Ignore the greens too; just to make me feel less guilty – ada makan sayur! Taste like ox tail curry ah 🙂

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NPC and Genetic Risk

Just this single month I attended two funerals of childhood friends who had suffered and died from nasopharyngeal carcinoma (NPC) or nose cancer.

This is a cancer that I know well and have seen up close as my first wife had also died from this disease. I have talked to the cancer doctors about the incidence of this cancer among Sabah natives and they said that clinical records definitely show that it is common among Kadazans, Dusuns and other inland natives of Sabah. My observations from sitting many many times in the waiting rooms of cancer doctors attest to this fact. (Perhaps my FB friends here who are MDs can second me on this.) In short, Kadazans and Dusuns have a relatively higher genetic risk of being afflicted with this disease. Why is this? The theory is that the genetic risk was originally from South China populations, and since many Kadazans and Dusuns have old (and for many, new—their great great parents are from China) South China bloodlines they carry this risk too. (See link below for a scientific discussion of this.)

The point for me to share this info is this: If you are in this high genetic risk group, be extra careful and watchful: If you feel something is not right inside your nose (the internal space between the tip of your nose and your eyes—the nasopharynx) and it persists for weeks, go see an ENT doctor! They have strobes to look into the space and can see if something is growing there – the cancer.

I have friends who caught it early, and after treatment, are still alive today, but sadly, I have also friends who were diagnosed late and have passed away. The very dangerous thing about this NPC is this: even if the cancer has just spread (has affected the nearby lymph nodes) the sufferer most probably only experienced mild discomfort (and not pain) and thus would not really give a serious thought to aggressively find out about his/her sickness/proper diagnosis. In other words, the absence of pain can lure you into a false sense of wellness.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013336/