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Menyampaikan obat ke tempat yang tepat

Target metode pemberian obat bisa berpotensi pada perkembangan yang lambat dari penyakit ginjal polikistik

Date:

June 25, 2015

Source:

University of California - Santa Barbara

Summary:

Untuk 12 juta orang di seluruh dunia yang menderita penyakit ginjal polikistik ( PKD ) , kelainan bawaan dengan tidak ada obatnya  , pilihan pengobatan baru mungkin hanya di awing-awang  . Metode pengiriman obat yang ditargetkan telah dikembangkan yang berpotensi memperlambat perkembangan penyakit ginjal polikistik .

......... Sekarang , Thomas Weimbs , seorang profesor di Departemen UC Santa Barbara Molekuler , Seluler , dan Perkembangan Biologi , telah mengembangkan strategi baru untuk menargetkan antibodi terapi untuk ginjal polikistik . Dia mencatat bahwa strategi membuka kemungkinan repurposing sejumlah besar obat yang ada untuk terapi PKD 

Terapi Antibodi  - kelas biologis - telah digunakan secara luas untuk mengobati berbagai penyakit kanker gangguan autoimun . Ini adalah terapi biologis menggunakan kelas antibodi yang disebut immunoglobulin - G ( IgG ) untuk mengikat dan mencegah aktivitas protein tertentu atau faktor pertumbuhan . Namun , di PKD , faktor pertumbuhan ditunjukkan untuk meningkatkan pertumbuhan kista berada dalam cairan terperangkap di ruang interior kista , yang disebut lumen , dimana antibodi IgG tidak memiliki akses ....more

Delivering drugs
to the right place

Targeted drug delivery method could potentially slow progression of
polycystic kidney disease

Date:

June 25, 2015

Source:

University of California - Santa Barbara

Summary:

For the 12 million people worldwide who suffer from polycystic kidney
disease (PKD), an inherited disorder with no known cure, a new treatment option
may be on the horizon. A targeted drug delivery method has been developed that
could potentially slow the progression of polycystic kidney disease.

.........................

For the 12 million people worldwide who suffer from polycystic kidney
disease (PKD), an inherited disorder with no known cure, a new treatment option
may be on the horizon.

PKD is a condition in which clusters of benign cysts develop within the
kidneys. They vary in size, and as they accumulate more and more fluid, they
can become very large. Among the common complications of PKD are high blood
pressure and kidney failure.

Now, Thomas Weimbs, a professor in UC Santa Barbara's Department of
Molecular, Cellular, and Developmental Biology, has developed a novel strategy
for targeting therapeutic antibodies to polycystic kidneys. He notes that the
strategy opens up the possibility of repurposing a large number of existing
drugs for PKD therapy.

Therapeutic antibodies -- a class of biologics -- are already being used
extensively to treat a variety of diseases from cancer to autoimmune disorders.
These biologic therapies use an antibody class called immunoglobulin-G (IgG) to
bind to and prevent the activity of specific proteins or growth factors.
However, in PKD, the growth factors shown to promote cyst growth reside in
fluid trapped in the interior space of a cyst, called a lumen, to which IgG
antibodies have no access.

Weimbs and his team have found a method that enables another class of
antibodies, immunoglobulin-A (IgA), to penetrate the cyst wall. The
researchers' results appear in theJournal of Biological Chemistry.

Weimbs, who has been working on PKD for more than a decade, had an aha moment
when he remembered his previous research as postdoctoral scholar at UC San
Francisco. This research dealt with the question of how IgA could cross a cell
layer by binding to polymeric immunoglobulin receptors (pIgR). Earlier work
Weimbs conducted at UCSB had shown that the transcription factor called STAT6
is overly active in PKD, and he also recalled that STAT6 had been shown to
drive the expression of pIgR in other organs.

"I put one and one together," Weimbs said. "I thought if
STAT6 is highly active in polycystic kidneys, maybe it also expresses a lot of
pIgR -- and that turned out to be the case. So we tested this in mouse models
and in human polycystic kidney tissues, and, in both cases, high levels of pIgR
were expressed in kidney cysts."

Weimbs and his team found that when they injected IgA into mice, about 7
percent of the injected IgA remained inside the cyst lumens of polycystic
kidneys. "This suggests that the IgA gets taken up and is trapped inside
because these cysts don't have an exit," Weimbs said. "So we end up
with a way of exploiting the pIgR system for targeting these antibodies
specifically to the polycystic kidney."

The key is using molecular cloning to reformat an existing IgG antibody to
IgA. Then the pIgR system carries the IgA antibody inside the cyst, where it
neutralizes a specific receptor.

"Our strategy allows for the repurposing of thousands of existing
monoclonal antibodies that have already been developed, which opens up a whole
new class of therapeutics not previously used for PKD therapy," Weimbs
concluded. "This paper is proof of concept that we can use IgA to target
polycystic kidneys. The next hurdle will be proof of therapeutic efficacy where
we actually take an IgA antibody targeted to a specific protein or growth factor
and see if it can inhibit cyst growth."







Story Source:

The above post is reprinted from materials provided byUniversity
of California - Santa Barbara. The original item was written by Julie
Cohen. Note: Materials may be edited for content and length.







Journal Reference:

1.   
Erin E. Olsan, Tamami Matsushita, Mina Rezaei, Thomas Weimbs. Exploitation
of the Polymeric Immunoglobulin Receptor for Antibody Targeting to Renal Cyst
Lumens in Polycystic Kidney Disease. Journal of Biological
Chemistry, 2015; 290 (25): 15679 DOI:10.1074/jbc.M114.607929

http://www.sciencedaily.com/releases/2015/06/150625161508.htm

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