Tuesday, December 11, 2007

Turning Mouse Tails Into Replacement Blood Cells for Sickle Cell Anemia

Induced pluripotent cells (iPS) have been garnering lots of attention (and papers) lately, since it was first shown that adult fibroblasts (and since then, skin cells) can be reprogrammed to pluripotency by forced expression of a handful of genes. Despite much speculation, it has remained unknown until now whether these cells are actually be good for anything, therapeutically speaking.

While it remains to be seen whether iPS can give rise to autonomous souls, Jaenisch's groups has now shown that iPS can be applied therapeutically. They derived iPS from the tail fibroblasts of sickle cell anemia mice, fixed their genetic deficiency ex vivo, differentiated them into hematopoietic progeintor cells and transplanted them back into the affected mice to restore a functional pool of red blood cells. Pretty damn cool.


4 comments:

kamel said...

Did you see Dr. Ellis' recent seminar on virus designs for stem cell gene therapy? It was basically three parts, the first dealing with retroviral gene therapy for sickle cell anemia. The final section was about engineering viruses to specifically infect pluripotent cells to use as a reporter for iPS cells.

Bayman said...

Yeah great talk. He also discussed transgene expression variegation following retroviral transduction of HSCs, a phenomenon I find very interesting. Definitely material for a future post if I ever get the chance...

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
Disorder

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B7GVW-4DS346T-1S&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=211981d545303693affebb8c012d2cac



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

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VS8-43DFJCH-G&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=10528ecbab3ec7e977301fb9f2688ef6



NIPRISAN -- Nix-0699 Toxicity Studies

http://www.biospace.com/news_story.aspx?StoryID=15890720&full=1


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

http://www.blackwell-synergy.com/doi/abs/10.1046/j.1365-2141.2003.04536.x?journalCode=bjh


NIPRISAN Case, Nigeria
A Report for GenBenefit (2007)

http://www.theparliament.com/NR/rdonlyres/F46A1A12-0A1A-41DA-9F5D-A11486CA9BFA/0/Nigerian_Case.pdf




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."

http://www.curetoday.com/backissues/v3n3/departments/specialreport/index.html



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
crises.

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.

http://www.fda.gov/CbER/gdlns/fsttrk.pdf



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.

http://xechemnigeria.com/products.htm


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.

NicosanForSickleCell@yahoo.com

Asclepius said...

United Nations Economic Commission For Africa

Book Of Abstracts

Science With Africa Conference

March 3-7, 2008

page 30



Evaluation of Niprisan (Herbal Medicine) for the Management of Sickle Cell
Anaemia

Charles Wambebe and Hadiza Khamofu, International Biomedical Research in Africa, Abuja,
Nigeria, wambebe@yahoo.com, Joseph Okogun, Nathan Nasipuri and Karynius Gamaniel,
National Institute for Pharmaceutical Research and Development, Abuja, Nigeria.


About 70% of all sickle cell anemia (SCA) subjects reside in Africa, estimated at over 12 million. The prevalence of SCA is estimated at over 2% while infant mortality is about 8% and survival rate of SCA babies in rural areas by five years of age is about 20%. These statistics indicate that SCA is probably the most neglected (and sometimes forgotten by health authorities) serious public health disorder with serious mortality and morbidity rates in Africa. The objective was to undertake pre-clinical and clinical assessments of a herbal extract vis-à-vis management of sickle cell anemia using Good Laboratory Practice and Good Clinical Practice principles respectively. In Africa, there is no standard treatment for sickle cell anemia, only palliative management is generally available. In view of this situation, most SCA subjects use herbal medicines. NIPRISAN is a standardized extract from four medicinal/food plants: Piper guineenses seeds, Pterocarpus osun stem, Eugenia caryophyllum fruit and Sorghum bicolor leaves. Short term toxicity study indicated that NIPRISAN was safe in laboratory animals. Bio-activity guided fractionation show that vanillin and aromatic aldehydes may be the bioactive moieties. NIPRISAN reversed sickled red blood cells and
protected them from being sickled when exposed to low oxygen tension. NIPRISAN dose-dependently delayed polymer formation of haemoglobin S. NIPRISAN induced 85% increased solubility of deoxy haemoglobin S. The in vivo efficacy study was undertaken at Children Hospital of Philadelphia, USA. Histological examination of lungs of control Tg transgenic mice carrying human sickle haemoglobin showed entrapment of massive numbers of sickled cells in alveolar capillaries. NIPRISAN significantly cleared the lungs of sickled cells. Furthermore, NIPRISAN induced profound effect on the survival time of Tg mice under hypoxic conditions (p<0.0001). The phase II clinical data indicated that all the subjects benefited from NIPRISAN with no serious adverse effect. About 80% of the subjects did not experience any crisis during the study (12 months). The subjects experienced significant reduction in hospital admission while attendance at school profoundly increased. Furthermore, there was no evidence of kidney or liver damage. NIPRISAN has been patented, licensed to an American company, registered and being manufactured at Abuja for global market.

http://www.uneca.org/sciencewithafrica/content/swa_book_of_abstacts-en.pdf


NICOSAN / NIPRISAN