Monday, November 19, 2007

The sickle cell gene's recent introgression into East Africa

This is a "Short Report" and it is indeed very short! It seems like they assume that patterns of mt-DNA and Y-chromosome diversity are not subject to forces of selection and just represent neutral "population-level forces". I wonder how safe this assumption is? Here is the basis of their test:
By typing both the haploid Y chromosome and the S gene in the same samples it should be possible to test for common demography as well as detect affinities of particular S variants observed in Sudan to other regions of Africa.
their conclusion:
Our results suggest that the sickle cell gene may have been preferentially introduced through males of migrating west African tribes (Figure 1), particularly Hausa-Fulani, and Bagara in the large migrations that began in the eighteenth century and escalated during the nineteenth and early twentieth century. The estimates of a recent figure of 1–3 generations for the introduction of the gene and associated haplotypes to eastern Sahel, is consistent with demography during the past 100 years and with a hypothesis of a recent origin of malaria as a major human infection.
"recent origin of malaria as a major human infection" - hmm...interesting!

Co-introgression of Y-chromosome haplogroups and the sickle cell gene across Africa's Sahel

Rihab E Bereir, Hisham Y Hassan, Niven A Salih, Peter A Underhill, Luigi L Cavalli-Sforza, Ayman A Hussain, Dominic Kwiatkowski and Muntaser E Ibrahim

European Journal of Human Genetics (2007) 15, 1183–1185;
Abstract: The Sahel that extends from the Atlantic Ocean to the Ethiopian highland is a historical reservoir of Africa's cultures and grandest populations and a known arena of ancient and recent migrations. We are interested in the issue whether such migrations were also carriers of genetic traits and whether this introgression could be associated with population genetic markers. Based on analysis of Y-chromosome haplogroups, we present evidence that the sickle gene, one of the major protective polymorphisms known in malaria, has in fact found its way only recently to the gene pool of the populations in eastern Sahel. We discuss the possible dynamics of the process and give estimates of the age of the introduction of the S allele into eastern Sahel.

1 comment:

Asclepius said...

NICOSAN for the Treatment of Sickle Cell Disease

There is a relatively new treatment for sickle cell being
produced in Nigeria by an American company called NICOSAN®,
it's proprietary name is NIPRISAN® . It was developed on
the premise of traditional Nigerian plant based medicinal
practices for the treatment of sickle cell disease.

It has been tested through phase IIb clinical trials and
found to be highly efficacious. Phase III trials have yet
to be completed however it was approved for sale in Nigeria
based on phase IIb trials and toxicity studies which showed
it to be safe and non-toxic.

Double-blind, placebo-controlled, randomised cross-over
clinical trial of NIPRISAN® in patients with Sickle Cell

Efficacy of Niprisan in the prophylactic management of
patients with sickle cell disease

NIPRISAN -- Nix-0699 Toxicity Studies

Niprisan (Nix-0699) improves the survival rates of
transgenic sickle cell mice under acute severe hypoxic

NIPRISAN Case, Nigeria
A Report for GenBenefit (2007)

This drug is a major advancement in the treatment of sickle
cell disease unfortunately it is not available in the U.S..
Although the compound has been granted orphan drug status
by the FDA and the regulatory body of the European Union,
to date investigational drug applications for the approval
process have yet to be submitted. Getting a drug approved
in either area is extremely expensive. Until there is
funding available to proceed with the FDA and EU
applications it will be difficult for non-Nigerians to
obtain the drug.

I do say difficult but it is not impossible. If you have a
hematologist or hemoncologist who is willing to put fourth
the effort there are special dispensations available
through the FDA for the importation of unapproved drugs on
a compassionate use basis.

"Expanded access program (EAP). EAPs are typically designed
to provide widespread access to a drug that has proven
efficacy in clinical trials but is still awaiting FDA
approval. They’re similar to standard clinical trials with
a specific treatment plan and certain FDA requirements, but
they have looser patient eligibility criteria. More than
23,000 U.S. cancer patients enrolled in an EAP for Iressa
before it was FDA-approved, for example."

"Single patient use. This program offers an experimental
drug to an individual patient, rather than a group. The FDA
approves these uses on a case-by-case basis. Decisions are
based on other treatments already available and information
about the drug’s efficacy and potential toxicities."

To date I have no knowledge that anyone has sought any
single use or expanded access from the FDA for Nicosan.
Unfortunately regardless of the dissemination of this
information thus far no one has put forth the effort to
obtain the drug for use.

If just one person would start the ball rolling with a
caring and concerned medical practitioner it could open up
the drug for wide spread use by tens of thousands of
patients across the U.S. Unfortunately thus far the general
response I receive is that people don't believe that their
physician would be interested in going to this sort of
effort nor do they themselves seem to be inclined to seek
the use of a treatment that could potentially end their

There has to be at least one physician out there who has
enough care and concern for his patients to be willing to
put forth the effort necessary to obtain this medication
legally. I urge anyone who is effected by sickle cell to
approach their physicians with this information and attempt
to obtain this treatment not only for themselves but for
all patients who could potentially benefit from it's use.

We already know the benefits of the treatments available in
the U.S. and the E.U.. In many cases they are only
marginally effective or in the case of hydroxyurea cause
side effects so serious that many choose not to use it as
treatment. Here we have an opportunity to use a treatment
that has been shown to be highly effective, eradicating
crises in the majority of patients and reducing crises by
50% in the most refractory cases.

Although the clinical trial group was what the casual
reader might interpret as quite small it is common for
drugs which fall into the orphan drug category to use small
sample groups. Many orphan drugs have been approved based
on very small phase II and phase IIb clinical trials in the
U.S. In the case of FDA fast track status, a drug may be
approved during phase II trials if the drug shows
significant advantage over current approved therapies for
life threatening illness.

Fast Track Designation is a program that, if granted, is
designed to facilitate the development and expedite the
review of new drugs, thereby allowing the FDA to approve
drugs used to treat a serious condition or a
life-threatening disease with less safety data following
the conclusion of phase II studies, rather than phase III,
the normal practice.

The main criterion for a Fast Track Designated drug is the
potential to treat a life-threatening illness or fill a
major unmet medical need. Fast Track may be submitted with
the IND or at any time during the clinical development of
the drug. The Fast Track designation may allow a company's
application to follow Priority Review, Standard Review, or
a Rolling Review of the application.

Nicosan by Western standards is an extremely inexpensive
drug. It is available in Nigeria without prescription at
$23/month for adults and child doses at $18/month.

Here is a link to the company and product website.

I sincerely hope that you find this information helpful. I
would encourage you to to forward and post this information
to any person, blog or website where persons effected by
sickle cell anemia can have access to this information.

Feel free to write me with any questions or you may have.

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